Best Tools for Gut Health & Weight Loss | Dr. Chris Thompson

Huberman Lab

Dr. Chris Thompson joins Andrew Huberman to explore the intricate relationship between gut health, the microbiome, and metabolic wellness. T

Key takeaways

• A lack of dietary fiber can cause gut microbes to consume the protective mucus layer, reducing essential butyrate production.
• Resistant starch (RS2) supplementation has shown promise in improving fatty liver disease and insulin sensitivity.

Main topics

• Gut Microbiome & Fiber
• Digestive Anatomy & Disorders

Notable quotes

Feed your microbes... if you're not feeding them fiber, they'll eat your mucus layer.

Conclusion

Maintaining a diverse microbiome through fiber and fermented foods is

Transcript preview

Speaker 1 (0:00) There's all sorts of evidence that if you don't have a lot of fiber, your microbiome's not healthy. Feed your microbes, you know, they need to be fed. And what they eat is fiber. Okay, that's what you want them eating. You want them eating fiber. And if you're not feeding them fiber, they'll eat your mucus layer. Okay, and we already talked about how thin that barrier is. And all of a sudden they start eating your mucus layer. They're not producing the butyrate you need, and the butyrate's needed to maintain the tight junctions, right? So there's layers to this. It's like a snowball effect that if you're not feeding the microbiome and keeping it healthy, you're going to run into all sorts of trouble. Speaker 2 (0:34) Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. Speaker 2 (0:43) I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Chris Thompson. Dr. Chris Thompson is a professor of medicine at Harvard Medical School. He is also the chief of interventional gastroenterology at Mass General Brigham in Boston. He is a renowned expert on the intersection of gastroenterology, metabolism, nutrition, and obesity medicine. And in today's episode, Dr. Thompson explains how to improve your gut health, including the roles of your diet, gut microbiome, and gastrointestinal motility, as well as how your gut communicates with the rest of your body, which of course includes the gut microbiome, but as you'll learn today, much more. Dr. Chris Thompson is a guest on this podcast because he's not just a GI tract and obesity medicine expert, he's also credited with having created an entire new field of treatments and perspectives on GI and metabolic health. So the knowledge she shares today is truly at the cutting edge and applicable, which is why by the end of today's episode, you will have a clear understanding of how your gastrointestinal system works, and you will have a set of new, modern, evidence-based tools for improving and maintaining your gut health. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, today's episode does include sponsors. And now for my discussion with Dr. Chris Thompson. Dr. Speaker 1 (2:12) Chris Thompson, welcome. Thanks so much. Good to Speaker 2 (2:14) be here. A lot of us hear these days about the gut microbiome, the gut-brain axis. We hear about GLP drugs that help people lose immense amounts of weight and stop feeling this food noise thing and on and on. But can we start by just having a conversation about this tube that is the digestive tract and get real basic and just educate people a bit on what happens that stimulates them to want to eat, why perhaps for certain periods of day or night they don't want to eat, and then what the passage of food through us. It looks like it is a series of steps. This is such a critical part of our biology and Speaker 1 (2:54) our lives. It's becoming more and more complex all the time, right? The gut and it does a lot of things. So Speaker 2 (3:01) it's Speaker 1 (3:03) obviously involved in digestion, but it's also an endocrine organ. You can hear it called the second brain, right? So there's a lot of different ways we think about the gut. And it is compartmentalized and each area has a different job. So at first you have, you know, the esophagus and his job is to just kind of. move the food into the stomach safely. And it's thick, right? It has different linings, so it can handle things that might be a little rougher. And it pushes sequentially, you know, down into the stomach. So it's taking that food bolus and driving it into the stomach. And you can have all sorts of problems in your esophagus, right? So each one of these organs has, you know, things it's supposed to do and then things that it doesn't do well. Sometimes people don't swallow well. It gets too tight at the bottom. There's Speaker 2 (3:41) a Speaker 1 (3:41) condition called achalasia. where it's just the bottom of the esophagus doesn't relax, right? And so we have procedures we can do in my line of work where you can tunnel down in between the layers of that esophagus. It's very thin, you know, a few millimeters. You can tunnel down into there and cut that muscle to relieve the obstruction. So Speaker 2 (3:57) what are the symptoms of that? So inability to swallow. So what do they do? They choke? Speaker 1 (4:01) Yeah, they'd feel like they're choking. So they'll swallow food. It'll get down and stop. And then they'll feel pressure. They'll feel really uncomfortable. If they drank some fluid with it, it might start coming back up. It'll just stay there. And then sometimes they'll have to induce vomiting to remove it. It's very uncomfortable for them. And it's not a terribly common condition, but it's becoming more and more frequent. I see it every week. So that inability to swallow. And you can get that inability to swallow for other reasons, actually, that are far more common. Chronic heartburn. If someone has reflux, that burning sensation, that can damage the lining of the esophagus. And it can lead to precancerous conditions called Barrett's esophagus, which is something that needs to be treated, looked at. and kind of followed. But with time, you can actually cause scarring. So you get a stricture. So it's kind of very fibrotic tissue there. That's another reason why people might have difficulty swallowing. There's other reasons as well that are more obscure. But so that's the job of that esophagus, just to move the food down safely. And a lot of times it doesn't work. Then you have the stomach next, right? First, what the stomach does is it stretches to accommodate and accept a meal, right? So it stretches. Normally, it's like a tube in your abdomen. But then when you start to smell food, it starts stretching and becoming more like a bag. Really, just the odor of food. Yeah, it can stretch, relax to accept that meal. And if it doesn't do that properly, it causes symptoms like nausea, right? So then it accepts the meal. And it has to do its job, which is to break it down and pass it on so that the stomach now isn't just transporting, it's breaking it down. And it does that mechanically. So the fundus, the top of the stomach, is holding that meal. That's what kind of stretched up to hold it. And then the rest of the stomach's working on it. So the body of Speaker 2 (5:43) the Speaker 1 (5:43) stomach, the next segment, is breaking it down, is grinding the food into smaller bits. Acid is part of this as well. The stomach secretes acid. And then the bottom of the stomach, called the antrum, will push the food out slowly into the duodenum. That's Speaker 2 (5:56) the Speaker 1 (5:56) first part of Speaker 2 (5:56) the Speaker 1 (5:56) small bowel. Satiety, satiation all becomes part of this because the stomach's what secretes ghrelin. And we'll talk about that probably more later, but the stomach secretes ghrelin. And so this is part of your satiety signaling. All sorts of problems with the stomach, right? So similar to the esophagus, food might not leave as it should in the right timing. So it can happen due to ulceration in the stomach, scarring, or something called gastroparesis. where for a variety of reasons, it might be post-viral, it might be due to diabetes, neurohormonal kind of origins of this. The stomach just doesn't empty as it should. People have nausea and vomiting with that and other problems. So then you get into the small bowel. And the small bowel job now, typically you do a little digestion still early on because you have pancreatic and biliary secretions going in there. But its main job is going to be to absorb calories, right? So that's absorbing calories and moving it down. It's very thin. It's one cell thick. It has about the surface area of like a pickleball court. One Speaker 2 (6:54) cell thick? Speaker 1 (6:55) Yeah, it's one cell thick. The lining is one cell thick. What's Speaker 2 (6:58) the Speaker 1 (6:58) cell type Speaker 2 (6:58) just to- Speaker 1 (6:59) Enterocytes, yeah. Those must be some Speaker 2 (7:02) really sturdy cells. Columnar epithelium, yeah. Speaker 1 (7:05) So they're pretty sturdy. They rely on more than just the cell itself to maintain that barrier. There's certain cells called goblet cells that produce mucin, and that creates a nice thick layer there that help. as another part of the barrier. They have something called tight junctions, right, between the cells, which are complex little structures that are part of that barrier as well. And there's immune cells in there. There's other elements to that barrier, but it is one cell layer thick. So that's why the stomach, the esophagus and stomach have got a good job of processing that food so that it's safe to go down through the small bowel and be absorbed. All sorts of issues with the small bowel. similarly you can have different diseases that affect that you know celiac disease uh crohn's disease etc different inflammatory conditions um and uh what we're learning now and we'll hopefully get get into is it plays a central role we think in metabolic disease and that's kind of what's very exciting is is its role in obesity diabetes and other similar conditions and then eventually have the colon. And that's where your microbiome is the star, right? The colon. Its job is to usually just absorb water. Most of the nutrients are gone by then. But it does play an important role as well. And it is working hand in hand with your microbiome to make sure that you're producing... It really is. It's mostly butyrate. I think that's mostly involved there where the microbiome is producing short chain fatty acids. And one of them, the most important probably is butyrate that has... a lot to say about your metabolism as well. That's involved in satiety signaling. And you have a lot of GLP-1 produced from the colon again. So you're getting these kind of endocrine function of your colon that's very involved and then it passes. So, and again, diseases in the colon, colon cancer is a big one, right? So colon cancer screening is important. People typically now, I think they move the age back to 45. Everyone should start getting screened and make sure they don't have cancer. You can do it. Different ways. There are genetic tests you can do like Cologuard. And if you do that, you have to do it every few years, but you can do that. You can do screening colonoscopy every 10 years if it's normal. And there's other things you can do as well. CT colonography is not as common in other tests, but those are the two most common. It's important to do that. How common is colon cancer? In our line of work, it's the most frequent cause of cancer, unfortunately. Speaker 2 (9:25) Are more people... being diagnosed because of more diagnostic procedures and are more people surviving colon cancer the Speaker 1 (9:33) survival rates are definitely improving due to screening programs right so that's that's important so it is definitely important to get screened also screening earlier helps so for instance starting at 45 is better than many people who started at 50 and they wouldn't get till 55 or 60 right but also if you have a family member that has had cancer you want to start at 40. Or if they were younger, you want to start 10 years younger than when they were diagnosed, right? So you want to start that screening process, really. It's very effective, you know, and it's important to do it. And I think that things like Cologuard and other genetic tests are going to keep getting better and help because you don't have to have that kind of very uncomfortable screening procedure. Colonoscopy is not a great way to do screening, right? You shouldn't have to have a relatively invasive procedure to be screened for something. You know, it should be something you do to a blood test or a stool study or something like that. And I think we're getting there with technology and that will definitely show dividends because you can have the colonoscopy to remove the lesion, which is something that we can do. It's a newer technique where we can actually go in and remove these very early cancers endoscopically. So we call it organ sparing surgery. So you don't have to actually remove a piece of the colon anymore. You can just kind of, you know, take the lining where that pre-cancer is residing. It's a complicated procedure, but it's easy for the patient. You know, they keep their colon, they go home the same day. these tests are easy ways to diagnose those patients and get Speaker 2 (10:50) them in for proper care. So very Speaker 1 (10:52) important. So that's pretty much the quick overview of the gut. And it plays, one thing we haven't touched on too much yet is its role in really satiety and kind of how it's involved in processing of food in detail and the kind of enteroendocrine system that's involved. Speaker 2 (11:12) I'd like to take a quick break and acknowledge one of our sponsors, Element. Element is an electrolyte drink that has everything you need and nothing you don't. That means the electrolytes, sodium, magnesium, and potassium, all in the correct ratios, but no sugar. Proper hydration is critical for brain and body function. Even a slight degree of dehydration can diminish your cognitive and physical performance. It's also important that you get adequate electrolytes. The electrolytes, sodium, magnesium, and potassium are vital for the functioning of all cells in your body, especially your neurons or your nerve cells. Drinking Element makes it very easy to ensure that you're getting adequate hydration and adequate electrolytes. My days tend to start really fast, meaning I have to jump right into work or right into exercise. So to make sure that I'm hydrated and I have sufficient electrolytes, when I first wake up in the morning, I drink 16 to 32 ounces of water with an element packet dissolved in it. I also drink element dissolved in water during any kind of physical exercise that I'm doing, especially on hot days when I'm sweating a lot and losing water and electrolytes. Element has a bunch of great tasting flavors. In fact, I love them all. I love the watermelon, the raspberry, the citrus, and I really love the lemonade flavor. So if you'd like to try Element, you can go to drinkelement.com slash Huberman to claim a free Element sample pack with any purchase. Again, that's drinkelement.com slash Huberman to claim a free sample pack. Today's episode is also brought to us by Lingo. Lingo is an everyday wearable that tracks your glucose 24-7. Glucose drives a lot of key processes that support energy, body composition, and long-term health. When glucose is constantly spiking and crashing, that's where we can start to see metabolic dysfunction. And over time, that can even progress to prediabetes. Right now, about 115 million adults in the U.S. have prediabetes. Most don't know it, and a higher percentage of men have it than women do. Often there aren't clear symptoms of prediabetes early on, so people don't tend to look into it. But the fact is that metabolic health is shaping how your body functions every day, whether you feel it or not. Tracking your glucose with lingo can help you see how food, activity, and stress impact your glucose throughout the day. I personally have used lingo, and it's been an invaluable tool for improving my metabolic health. If you would like to try Lingo, Huberman Lab listeners in the US and UK can save 10 % on a four-week plan. Just visit hellolingo.com slash Huberman for more information. Terms Speaker 1 (13:35) and Speaker 2 (13:35) conditions apply. Again, that's hellolingo.com slash Huberman. Speaker 1 (13:40) A Speaker 2 (13:40) couple questions that no doubt will resonate with people because they're fairly common and you'll tell me if they're of concern or not, depending on the frequency. We'll start at the top of the GI tract. People will say sometimes that they eat and some of the food seems to go up their nose. They know this because if they blow their nose, they might get some food particulate. It sounds like something that's not entirely uncommon based on the number of questions I get about it. What's going on there? Why would... you know i get asked a lot of questions some of them truly weird and rare and some of them um weird and less rare and i would put it in the second category Speaker 1 (14:14) That could be a variety of different things. And this is the area that I do work in, right? So it can be an oral pharyngeal transfer problem where the hypopharynx is transferring food into the esophagus. That can be an ENT thing. It can actually be functional medicine as well, where you can work with a speech pathologist that teaches people how to swallow better. They might have to change the quality of the food they're eating, the thicker food. They might have to turn a certain way to swallow. And there's ways they can actually train people with kind of biofeedback to learn how to swallow better because that part's still under your control. control a little bit. They're not swallowing well. Yeah. And with age, that can happen, right? With age, that can happen. Now, the next thing that can contribute to that is if they have high tension in the first sphincter up above, which is the upper esophageal sphincter. That's the sphincter that separates the top of your esophagus from your mouth, basically. And that can have high tension. And what I see a lot is something called Zenker's diverticula, which we haven't talked much about. There's a few different little pockets that can form high up in your esophagus near that sphincter. There's different names for how they, you know, kind of where they exactly occur. And with time and with age, this is like a herniation of mucosa through the muscle and it creates a pocket and that can actually trap food. So when people are eating, the food goes into the pocket and then comes back up and can go out their nose or sit in there, which is very uncomfortable for them, right? That's another way you can have problems swallowing. And that can be fixed very easily. We go in through the mouth, actually make a tiny incision and just kind of take down the septum. that's part of that pocket opening up the pocket so that the food can leave. So it's important to do it early too, because people can actually, this, it looks like an inconvenience initially, right? It's, you know, you're not swallowing well, food, you know, is not where it's supposed to be necessarily. The problem is when people then aspirate and that food goes in the lung, and then it can lead to scarring in the lungs, and eventually it can really cause problems. So it is something that should probably be taken seriously and looked at, even though it sounds funny, you know, it is something that can be a real problem. Speaker 2 (16:08) There's a weird thing about GI tract and bowel movements in particular, which is the following. With babies, with puppies, and to some extent with ourselves, but especially with babies and with puppies, because they can't speak, we have a couple of key readouts that we intuitively understand reflect their health. One is the color of their skin, the eyes, like if eyes are looking glassy or tired, you know. And the quality or lack thereof of their bowel movements, quality, frequency, et cetera. But then something happens where speech comes online and we get, you know, toilet trained. And then everyone's responsible for like understanding like their own bowel movements, right? And then we're never really told like what's healthy bowel movements. But we all kind of know what's normal for us or not normal. I'd be lying if I didn't say like these are important metrics of health. Speaker 1 (17:04) Yeah. Well. there's so much you can tell from bowel movements. Okay. So the rule of thumb is, you know, you don't want to have more than three a day and you don't want to go longer than three days without having a bowel movement. So that's kind of the general rule. And you want it to be one formed bowel movement, you know, or a couple, you don't want little tiny pebbles that's called scabulous stool. And that's, that's a sign something's going on, but there's a lot you can tell how much are they taking enough fiber, right? World Health Organization. uh published something in the lancet years ago on fiber a fiber synthesis i think they called it and they found that you know the vast majority of population really doesn't especially western countries just are not getting enough fiber which is obviously concerning because it that that causes a lot of issues long term right which which we'll get into But if you're having these scabulous stools, if you are constipated, meaning you're having a bowel movement more than once every three days, and they're hard stools, that's a sign you're not getting enough fiber. So that's one thing you really have to think about, right? Additionally, there's other things you can tell after procedures. You know, if a bowel movement's very dark, tarry, and shiny, that's a sign you have blood in your GI tract, right? So there's different things you can tell from the stool that are important to keep an eye on. In general, that's kind of the rule of thumb with bowel movements. Having more than three a day is probably leaning towards being too loose, right? And if you're not having one every three days, you're probably bound up. And then you really have to think about fiber. As Speaker 2 (18:28) I recall, the recommendations were for adult men, 35 grams of fiber per day, and for women, 25. And obviously, that's not accounting for variations in body weight and height and all the rest. So does that sound about right? Speaker 1 (18:41) Yeah, that's about right. And it kind of depends on the quality too. There's a couple of other really interesting studies that came out recently, just within the last few years, looking at the importance of fiber related to certain conditions. Like one was fatty liver, right? And fatty liver was an interesting study. They were using resistant starch, like level two. So basically raw powdered potatoes, something like that, right? Speaker 1 (19:08) they were supplementing it i think it was at 40 grams and they found that when they did that they actually saw significant improvement in fatty liver which is phenomenal right and it was you know relatively weight stable so it has important treatment effects another group actually um studied it and looked at insulin sensitivity so they did clamp studies you know where they they would um kind of really be able to detect insulin resistance and kind of try to look at um kind of glucose utilization clearance. And they found that with this RS2 type, you know, resistant starch too, they were able to improve insulin resistance and insulin sensitivity as well. So fiber is very important. It's not just about the bowel movements, right? It's also about, you know, really just having, you know, health. It probably helps the microbiome. There's all sorts of evidence that if you don't have a lot of fiber, your microbiome's not healthy, right? You get less diversity in your microbiome. the different studies that have looked at that it is important to have that fiber and that constipation is an early window into it right it's an early sign maybe you're not getting enough enough Speaker 2 (20:12) fiber yeah i make it a pointy fruits and vegetables because i like them but recently i started supplementing with a powdered psyllium husk that and some of them actually taste pretty good and my expectation is i was going to feel really bloated it was quite the opposite it not that i had gut issues before if it was normally kind of like hyper normalized things actually it made uh post meal uh subjectively the sensation just like feel good feel great um and i didn't expect that i thought okay more fiber i think a perception people have is like more fiber more regularity and more bloat and i think that's a that might be true for some people but it certainly wasn't my experience and i think that if i feel like the messaging on fiber to the general public is pretty lousy meaning people are told to take it that's great they're told all the time but i think people think oh if i have a lot of fiber i'll be really gassy i'm going to be really bloated as you point out it's not just about regularity and speed of digestion it's about creating a healthy milieu for the gut i think if more people knew that they probably make a move to consume more fiber. Totally. Speaker 1 (21:16) It's like feed your microbes, you know, or they're going to eat you, right? And it's kind of true, Speaker 2 (21:20) right? Because they Speaker 1 (21:21) need to be fed. And what they eat is fiber. Okay. That's what you want to be eating. You want to be eating fiber. And if you're not feeding them fiber, they'll eat your mucus layer. Okay. And we already talked about how thin that barrier is. And all of a sudden they start eating your mucus layer. They're not producing the butyrate you need, and the butyrate's needed to maintain the tight junctions, right? So there's layers to this. It's like a snowball effect that if you're not feeding the microbiome and keeping it healthy, you're going to run into all sorts of trouble. Speaker 2 (21:49) Raises some interesting questions about intermittent fasting. I think very few people are doing long-term fasts of more than a day or so. I mean, it does happen, but most people, a lot of people do sort of time-restricted feeding or they'll skip breakfast. I'm one of those people most days just by default. I had a colleague, friend at Yale who studied microbiome. And I said, oh, so does fasting improve the gut microbiome? And he said, no, actually during the fasting period, your microbiome starts eating up your digestive tract, which is what you're saying. But then he said, but then the rebound often is, puts you at a slightly better place afterward. So it's tricky. Should people avoid intermittent fasting if they're having gut issues? I know we don't want to make any broad recommendations. It's highly contextual. But based on what you said, it seems that it stands to reason that you might want to avoid having your stomach empty for very long periods of time outside of sleep. I Speaker 1 (22:43) don't see it as being a major issue. I think the benefits of intermittent or time-restricted eating, intermittent fasting, probably would outweigh that risk. You know, you need to give your pancreas time to relax. You know, you need to have insulin come down. If you're eating frequently, your insulin levels are already up, always up, and that causes problems. So I do think the benefit of the time-restricted eating definitely outweighs that potential risk. Great Speaker 2 (23:10) to hear, especially as somebody who just by default doesn't eat breakfast or just... Don't get hungry till 11. I Speaker 1 (23:15) skip breakfast as well. But there's studies because initially they actually used to say, well, you have a cortisol spike in the morning and, you know, you're more likely to store the food you take in if you eat in the morning. Turns out maybe that's not so true. It might be better to actually have, you know, eat earlier and then have your fasting window start in the afternoon. I think doing is better than not doing it. I still skip the Speaker 2 (23:37) breakfast. The topic of fermented foods, low sugar fermented foods as a possible benefit for gut health is. come up since justin sonnenberg and colleagues have published that the study it there's a small number of people in that study admittedly but um that taking in some low sugar fermented foods really helped lower the inflammatome they didn't look specifically at as i recall uh symptoms of gut irritability irritation or things of that sort but what are your thoughts on from low sugar fermented foods so we're not talking beer we're talking kimchi sauerkraut Speaker 1 (24:10) I Speaker 2 (24:10) think they're Speaker 1 (24:11) important and they're missing in the Western diet, which is an issue. And I think the study you referred to, actually, I think they compared it to fiber, right? It was fermented foods to fiber. And with the fermented foods, you had reclaimed some diversity in the microbiome, which was great, as well as the reduced inflammatory markers, where the fiber didn't seem to do that. And you saw all these benefits in these other fiber trials that we're talking about with the resistant starches, right? It stands to reason that we'd probably see that as well as we do more research in the fermented foods. They're beneficial for a variety of reasons. One, they're prebiotic, right? So you're feeding your microbiome things they want, which is phenomenal. It's already kind of started. It's a little partially digested, which is really helpful. And they're also a little bit of a probiotic as well because you do have some live cultures in there, right? And you usually have bifidobacterias or lactobacillus or something like that in them and a variety of other things as well. So it gets the ball rolling, right? So it's sort of like when you're trying to grow something, you want to plant the seeds, but also have the fertilizer and whatnot. And this is what fermented foods do for you. So I think, you know, that's very helpful. It's all about maintaining this kind of healthy microbiome that can produce things like butyrate, which have a lot of benefits we can talk about. You can't just take butyrate and then it's not going to make it to the colon, right? It needs to be in the colon to have its effect. And so what these bacteria do is they kind of cross-feed in a sense, right? So you have those first layer of bacteria that will take the fiber and break it down and they create acetate and lactate and whatnot. And then that... can then be used by other bacteria. So you're feeding the other bacteria that can then turn that into butyrate and things like that. The butyrate is magical, right? So that will feed your colon cells. Your colon cells live on that with butyrates needed for those tight junctions. Butyrate does all sorts of things via GLP-1 pathways and satiety pathways. So it has a lot of different... roles that it's playing additionally it keeps your bowel acidic right so like these short chain fatty acids and you know acetate and whatnot and that's great to to make sure you are protected from certain pathologic organisms might want to take take root right so the aerobic organisms and the the other organisms that you don't want don't survive as well in an acidic environment so Really important to take these fermented foods in addition to fiber. Do you make it a point to consume them? I do, yeah. I like kefir and everyone will say that. I like that. I think it's phenomenal. Yeah, it's good. Kimchi is good. Sauerkraut. There's all different types. Yogurt. There are different types, I think, that everyone should be able to find. Kombucha. And it's certainly missing in our diets. So I think it's important to... to recommend that the folks do? Canker Speaker 2 (27:12) sores and ulcers, my understanding for a long time is they were caused by stress or wounds to the mouth. And then, you know, a couple of folks won a Nobel Prize for identifying a soil-based bacterium that causes ulcers. And I loved that Nobel Prize year, you know, as a scientist, like some people watch the Super Bowl, like, you know, we're like, who won the Nobel Prize? And it's never surprising who wins. It's at least for the sciences, right? often surprising who doesn't but let's leave aside that that component but that was a very surprising set of findings right like a gut bacterium is causing ulcers and i love the findings but at the same time i think many many millions of people hundreds of millions billions across history would say stress gives people ulcers so there's something going on there that's more than soil-based bacterium, right? Yeah, Speaker 1 (28:02) definitely. And Speaker 2 (28:03) that's the problem with these, you know, the way the media covers these findings, like it's not all that you ingested the wrong soil. I mean, stress can give you ulcers, right? Or am I missing something? Speaker 1 (28:13) Stress can play a role. You know, it is certainly complicated. Barry Marshall was phenomenal in Australia and he found H. pylori could cause gastric ulcers, right? And he had to consume, no one believed him. He had to consume himself, consume it. And then he had gastric ulcers. I love it when Speaker 2 (28:29) scientists do self-experimentation. That's crazy, right? But that was phenomenal, Speaker 1 (28:32) right? And he proved H. pylori and we need to treat that, right? And actually H. pylori was actually found even in Otzi the Iceman. I don't know if you remember Otzi the Iceman. He was this... Five thousand year old, you know, Homo sapien in the Italian Alps, he was found frozen, right? So you could actually get into his stomach and see what was in there. He Speaker 2 (28:51) died stressed. Speaker 1 (28:51) He died stressed. Speaker 2 (28:52) He had H. pylori in his stomach. That thing's been around a long time. Speaker 1 (28:55) It's kind of interesting. There's other lessons there, like a loss of diversity of the microbiome, right? With industrialization, we have far fewer species and less genetic diversity in our microbiome. But regarding ulcers, so I actually did, study this in gastric bypass patients a good bit, right? And it was not a bacterium that was causing it, right? Sometimes it was a relative ischemia. Type 2 diabetes causes kind of microvascular ischemia. Smoking can cause microvascular ischemia. In gastric bypass patients, the small bowel doesn't, it's a distal part of the small bowel from lower down that's connected to the stomach and it doesn't have bicarbonate. that's being secreted from the pancreas in the area. So there's no way of neutralizing acid. So if the pouch, which we can get into the anatomy here, but if the pouch of the gastric bypass is too large and makes acid, the duodenum now has no, or the jejunum actually, has no natural defense against that. So acid clearly plays a role. And if you're stressed, it can produce more acid, right? So generally there's probably multiple hits. We don't fully understand things, but clearly it's not just an infectious organism. And it kind of depends on individual circumstances and susceptibilities. But ulcers are certainly something that can occur short of a bacteria. So Speaker 2 (30:12) important for people to hear that, you know, because one thing can cause something, it doesn't mean it's always the case. So let's talk about metabolic health, hunger, obesity, weight loss. These are areas that, you know, square in your wheelhouse. Can't have this conversation without talking about the GLPs. Most everyone has heard of these things nowadays. Millions and millions of people, I've heard, I don't know if this is true, as many as 20 % of people 18 and older have taken or are currently taking a GLP or either, you know, Zempic, Monjaro, soon Redditor, TrueTide will be out to market. What's your thought on these compounds? Are they the perfect solution to weight loss? Well, Speaker 1 (30:52) I'm grateful we have them, right? Obesity is a serious problem. And all the metabolic issues. that are kind of there with obesity need to be addressed. And we weren't doing much with it, unfortunately, until the GLP-1s came around. So GLP-1s are fantastic from that standpoint. They're not perfect, you know, there's limitations, but it's much better to have them than not have GLP-1s for sure. There's issues with certainly adherence, unfortunately, right? So there's a number, over a million people a month are coming off GLP-1s, right? And it's for a variety of reasons. About 30 % come off GLP-1s in the first month and then 50 % or so by the end of the year, right? And it's not specific to GLP-1s. You see that with any medicine. You see that with blood pressure medicines. You see that with cholesterol medicines. Speaker 2 (31:43) Can we say what the primary driving force is in the case of GLP-1s? Is it the side effects? Is it they don't Speaker 1 (31:50) like having to pin themselves? I think because the numbers are so curiously similar to all the other medicines, maybe there's some underlying thing where people just don't like taking medicines frequently. That tracks. That might be part of it. I think that sticking yourself is probably for some people. They don't want to jab themselves once a week. That might be something, needle fatigue. That's probably there. I think when you take a medicine orally every day, it gets hard to remember to take it. And then I think there are issues with how you ramp them up to the effective dose and side effects. I think there's ways you can do that. you know, safely going step by step. But nausea is an issue with some of these, you know, muscle loss is an issue. There's different features there. And then additionally, you know, long-term this, this is, you know, you're taking a super physiologic dose of something and we don't know what the long-term ramifications could be. So even though I believe the benefits outweigh the costs, right? You're treating obesity. We know obesity is a problem. We don't know, you know, GFP wants to be a problem long-term. That does weigh heavy on some people's minds, and that might be why they stop as well. So in my practice, where we do endoscopic therapies, over 85 % of people have already been on a GLP-1, and either they're struggling on it or they've come off. Speaker 2 (33:00) 80? 85%. Wow. Yeah. Again, we don't want to get too far into the sociology and psychology of medication adherence, but it is interesting that so many people come off. But then there were meds like SSRIs and things like that, which I think can benefit certain people, like people with full-blown clinical OCD. They've been extremely, they've saved lives, right? But then they're over-prescribed. I feel like, especially in the United States, people like their prescription drugs. So if they're stopping, I feel like there's got to be a reason. I mean, aren't we the biggest consumer of prescription drugs in the whole world? Like, people love their drugs. That's Speaker 1 (33:39) true. Speaker 2 (33:39) I've heard about the nausea. I don't Speaker 1 (33:41) know. Speaker 2 (33:42) There are Speaker 1 (33:42) a Speaker 2 (33:42) number of people now who are, quote unquote, micro dosing the GLPs and finding that they're getting some benefits without taking the prescribed amount. I'm not recommending people do that. You know, I guess talk to or don't talk to your doctor. They probably won't approve. But I know people are doing that. I think initially it was because of cost and actually pen sharing, but also people feeling like, oh, I get the same effect. So is your sense that when because the way clinical trials are done, there aren't. Often there aren't like really nice dose responses that you're just kind of comparing. They're so expensive to do these trials that they're going, you know, two doses, you know, moderate high versus placebo. And then that's what the doctors have to work from. Do you have any knowledge of whether or not the lower dosing brings, takes people away from side effects and then you're seeing fewer of them? I Speaker 1 (34:31) think it's actually very useful. So that's, you know, the approved dosages are kind of just, an effect of our regulatory system, as you've alluded to, right? And it's too expensive to do different doses. Plus, it takes away personalization. You know, we're all trying to get to precision medicine and personalized medicine. And that's what microdosing allows you to do. And the first time I heard about microdosing was one of my patients. And he was a physician. And he came in and he said, you know, I... A, it's too expensive. B, I don't feel great on it. And C, I'm doing this thing where I take the pen and I inject it into a sterile vial and I use an insulin syringe and I'll take a small amount out and I'll give it to myself. And he said, I'm doing great. I don't feel nauseous. My weight is staying off. And he was a physician, so he was familiar with the equipment, if you will. And that was the first time I came across it. I was like, wow, that's actually, that's a great idea. A lot of my patients actually do microdose these things. And generally you get up to the point where you want to lose weight, you get to that dose, you're losing weight, you're losing weight. And then for maintenance, rather than just stopping it, because if you stop the GLP-1s, there's problems, right? This is not meant to be stopped. These are kind of lifelong medicines. Instead of stopping it, just go to microdosing and you'll find a spot, hopefully, not everyone does, but you'll find a spot where you keep the weight off, you feel good, and you're not taking as much of the med. Now, The problem with coming off of them is, especially with the original drugs, you know, like semaglutide is an example, right? Where when you lose weight, about a third of the weight you lose would be lean mass, right? So most muscle, right? Maybe some bone, et cetera. And the problem is when you cycle on and off, right? So say you come off of it and you put your weight back on, you're not putting the lean mass back on, okay? You're putting the fat back on. So now you've shifted your body composition to be less favorable than before you were on the GLP-1. And then you go on it again and you lose weight again and you lose a little more muscle. And then you go off and you put more fat on, not more muscle. So now basically you're taking your body composition and shifting it worse every cycle. So there has to be a game plan. If you're coming off the GLP-1, you need either to microdose it or have a bridging plan to a procedure or something else, which will keep the weight off for you. Speaker 2 (36:46) Are there any good studies showing that resistance training can offset the muscle loss? um from a standard or microdose of of one of these glp drugs yeah Speaker 1 (36:56) resistance training definitely i i'm not familiar with one that was the primary outcome of the focus right but you can actually see that that does play a major role in maintaining muscle and that's with anything it's not just glp1 medications it's with the first generation medications it's with any surgical procedure or endoscopic weight loss procedure you know, if you're doing resistance training, you tend to maintain your muscle because the body realizes, I need this muscle. I'm not going to get rid of it as a person losing weight, right? So when there's a caloric deficit, the body is looking for what it can do to, you know, to maintain, you know, energy levels, if you will. And you don't want it chewing up the muscle